The term “poloxamer” refers to a class of polyoxyethylene-polyoxypropylene-block copolymers (first mentioned in U.S. Pat. No. 3,740,421), which are also known under the trade name “Pluronic®” or “Lutrol®” (trademark of BASF SE). These are block copolymers consisting of hydrophilic polyethylene glycol outer blocks and hydrophobic polypropylene glycol inner blocks, i.e. (poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide)-tri-block copolymers, which can be broadly summarised by the following structure:

These block copolymers form sols or gels in water by phase separation: The polyethylene glycol blocks dissolve in water, while the polypropylene glycol blocks become associated with one another. This process is called micelle formation. While the micelles are present in a relatively disordered state at a lower temperature (sol state), an ordered formation of these micelles is brought about when the temperature increases, which results in the solidification of the liquid (gel state) (see Alexandridis P., Holzwarth J. F., Hatton T. A. Micellization of Poly(ethylene oxide)-Poly(propylene oxide)-Poly(ethylene oxide) Triblock Copolymers in Aqueous Solutions: Thermodynamics of Copolymer Association. Macromolecules. 1994; 27(9):2414-25). Such gels are therefore also referred to as thermoreversible hydrogels.
Hydrogels based on poloxamers have been known for quite some time (cf. J., Swafford W. B.: Pluronics as a suppository base. Am. J. Pharm. Sci. Support. Public Health. 1960; 132:301-303). Moreover, a chain-extended polymer of poloxamer 407 (Pluronic® F 127) and hexamethylene diisocyanate (HMDI) has been described (cf. Jiang J., Malal R., Li C., Lin M. Y., Colby R. H., Gersappe D., Rafailovich M. H., Sokolov J. C., Cohn D.: Rheology of Thermoreversible Hydrogels from Multiblock Associating Copolymers. Macromolecules 2008; 41:3646-3652).
Since poloxamers are biologically inert, they were soon used as suppositories for pharmaceuticals and, with the emergence of regenerative medicine, also as cell carriers (cf. Kamil S. H., Eavey R. D., Vacanti M. P., Vacanti C. A., Hartnick C.: Tissue-engineered cartilage as a graft source for laryngotracheal reconstruction—A pig model. Arch. Otolaryngol. 2004; 130(9):1048-1051).
The particular advantage of these hydrogels resides in the described thermo-sensitive behaviour. A minimally-invasive application of incorporated cells is thus conceivable. The latter can be easily introduced in the liquid state. After implantation, gel formation occurs due to the change in temperature, which causes the cells to be maintained at the desired location (cf. Cohn D., Lando G., Sosnik A., Garty S., Levi A.: PEO-PPO-PEO-based poly(ether ester urethane)s as degradable reverse thereto-responsive multi-block copolymers. Biomaterials 2006; 27(9):1718-1727; Nguyen M. K., Lee D. S. Injectable biodegradable hydrogels. Macromol. Biosci. 2010; 10(6):563-579).
The use of thermoreversible hydrogels is advantageous, for example, in the treatment of burns. The hydrogel allows the transdermal or local delivery of an active substance and maintains a high degree of moisture on the surface of the skin. This prevents dehydration. In addition, the hydrogel adheres to a considerable degree to the damaged tissue and has a certain elasticity, thereby avoiding a separation of the hydrogel and absorbing, at the same time secretions emerging from the wound. Generally, hydrogels promote healing, as they pass quickly to the gel state at the wound site and maintain moisture in the wound.
While most poloxamers with low polymer concentrations only form gels with poor mechanical properties, chain-extended poloxamers achieve greater stability of the gels. Initial attempts to extend the chains were performed with acrylic acid esters (acrylates). This causes linking moieties with C═C double bonds to the poloxamer. Thereafter, chemical addition reactions were carried out so that a plurality of poloxamer moieties could be connected. Derivatives of acrylic acid are physiologically not harmless. If the chain extension is performed by diisocyanates, the individual poloxamers are linked by urethane moieties. Polyurethanes have been used for a long time as medical implants owing to their tissue compatibility. A further disadvantage to date has been the lack of biological recognition of the material by the cells, which were up to now unable to adhere to the material.
It is thus the object of the present invention to provide chain-extended hydrogels based on poloxamers which do not have the known disadvantages of the prior art, and which are suitable for medical applications. It is further the object of the invention to provide thermoreversible hydrogels which are capable of releasing a biologically-active agent or active substance. In addition, it is the object of the invention to provide thermoreversible hydrogels containing biological material and living cells, wherein the cells adhere to the biological material, and therapeutic applications therefor.